Hypertrophic cardiomyopathy is the most common inherited heart disease and is the most important cause of sudden death in the young. Recently, a gene which controls the production of the main protein of the heart, beta myosin heavy chain gene, located on chromosome 14, has been linked to the disease in some kindreds with hypertrophic cardiomyopathy, We have found distinct mutations in the beta myosin heavy chain gene in several kindreds with hypertrophic cardiomyopathy. We have also shown that although the disease affects the heart predominantly, the cardiac protein is also expressed in skeletal tissue and that the mutant RNA and protein are also to be found in skeletal muscle. This has led us to determine whether the mutant protein in skeletal muscle has demonstrably abnormal function. The in-vitro motility assay measures the velocity of fluorescently-labelled actin filaments as they slide along myosin molecules bound to nitrocellulose-coated surface, allowing analysis of the enzymatic-mechano activity of the beta myosin. The motility activity of myosin from skeletal sample from patients with two distinct mutations were significantly less than control subjects. Thus, for the first time distinct mutations in the beta myosin heavy chain gene have been shown to result in skeletal protein with abnormal function.